Tuberculosis (TB) is a chronic infectious disease caused by infection with Mycobacterium tuberculosis and other Mycobacterium species. It is a major disease in developing countries, as well as an increasing problem in developed areas of the world. More than 2 billion people are believed to be infected with TB bacilli, with about 9.4 million new cases of TB and 1.7 million deaths each year. 10% of those infected with TB bacilli will develop active TB, each person with active TB infecting an average of 10 to 15 others per year. While annual incidence rates have peaked globally, the number of deaths and cases is still rising due to population growth (World Health Organisation Tuberculosis Facts 2010).
The mycobacterial protein Rv1196 (described, for example, by the name Mtb39a in Dillon et al Infection and Immunity 1999 67(6): 2941-2950) or fragments or derivatives thereof are protein antigens of potential benefit for the treatment or prevention of tuberculosis. Rv1196 is highly conserved, with 100% sequence identity across H37Rv, C, Haarlem, CDC1551, 94-M4241A, 98-R6041NH-RIF-EM, KZN605, KZN1435, KZN4207, KZNR506 strains, the F11 strain having a single point mutation Q30K. Rv1196 is a component of the fusion protein antigens Mtb72f and M72 (described, for example, in international patent application WO2006/117240).
The formulation of protein antigens is extremely important in order to ensure immunogenicity is maintained. Immunostimulants are sometimes used to improve the immune response raised to any given antigen. However, the inclusion of adjuvants into an immunogenic composition increases the complexity of preparation of the components as well as the complexity of distribution and formulation of the composition. The preparation of each of the adjuvant components as well as the antigenic component must be considered by formulators. In particular, the compatibility of the antigenic component with the adjuvant component should be considered. This is particularly the case where lyophilised antigens or antigenic preparations are intended to be reconstituted with an adjuvant preparation. In such a circumstance, it is important that the buffer of the adjuvant preparation is suitable for the antigen and that immunogenicity or solubility of the antigen is not affected by the adjuvant.